Loss of Grainy Head-Like 1 Is Associated with Disruption of the Epidermal Barrier and Squamous Cell Carcinoma of the Skin

Download
Author
Mlacki, M; Darido, C; Jane, SM; Wilanowski, TDate
2014-02-20Source Title
PLoS OnePublisher
PUBLIC LIBRARY SCIENCEUniversity of Melbourne Author/s
Darido, CharbelAffiliation
Sir Peter MacCallum Department of OncologyMetadata
Show full item recordDocument Type
Journal ArticleCitations
Mlacki, M., Darido, C., Jane, S. M. & Wilanowski, T. (2014). Loss of Grainy Head-Like 1 Is Associated with Disruption of the Epidermal Barrier and Squamous Cell Carcinoma of the Skin. PLOS ONE, 9 (2), https://doi.org/10.1371/journal.pone.0089247.Access Status
Open AccessAbstract
The Grainyhead-like 1 (GRHL1) transcription factor regulates the expression of desmosomal cadherin desmoglein 1 (Dsg1) in suprabasal layers of the epidermis. As a consequence, the epidermis of Grhl1-null mice displays fewer desmosomes that are abnormal in structure. These mice also exhibit mild chronic skin barrier defects as evidenced by altered keratinocyte terminal differentiation, increased expression of inflammatory markers and infiltration of the skin by immune cells. Exposure of Grhl1 (-/-) mice to a standard chemical skin carcinogenesis protocol results in development of fewer papillomas than in wild type control animals, but with a rate of conversion to squamous cell carcinoma (SCC) that is strikingly higher than in normal littermates. The underlying molecular mechanism differs from mice with conditional ablation of a closely related Grhl family member, Grhl3, in the skin, which develop SCC due to the loss of expression of phosphatase and tensin homolog (PTEN) and activation of the phosphatidylinositol 3-kinase (PI3K)/AKT/mechanistic target of rapamycin (mTOR) signaling pathway.
Export Reference in RIS Format
Endnote
- Click on "Export Reference in RIS Format" and choose "open with... Endnote".
Refworks
- Click on "Export Reference in RIS Format". Login to Refworks, go to References => Import References